Tislelizumab Plus Chemotherapy Extends PFS and OS in Nasopharyngeal Carcinoma

Findings from the phase 3 RATIONALE-309 trial (NCT03924986) demonstrated that tislelizumab (Tevimbra) plus chemotherapy delivered sustained progression-free survival (PFS) and meaningful overall survival (OS) improvement vs placebo after a 3-year follow up in patients with nasopharyngeal carcinoma.¹ Investigators reported a median PFS of 9.6 months (95% CI, 7.6-11.6) for patients in the experimental arm vs 7.4 months (95% CI, 5.6-7.6) for patients in the control arm (HR, 0.53; 95% CI, 0.39-0.71). The median OS was 45.3 months (95% CI, 33.4-not estimable [NE]) vs 31.8 months (95% CI, 25.0-NE), respectively (HR, 0.73; 95% CI, 0.51-1.05).

A total of 326 patients with confirmed recurrent or metastatic nasopharyngeal carcinoma were evaluated and were randomly assigned to receive either tislelizumab plus chemotherapy (n = 131) vs placebo plus chemotherapy (n = 132). The primary end point was PFS or death from any cause, whichever occurred first. Secondary end points included OS, PFS after next-line therapy, and safety.

Trial Design

Between April 18, 2019 and September 30, 2020, treatment-naïve participants with histologically or cytologically confirmed recurrent or metastatic NPC were randomly assigned 1:1 to receive tislelizumab, 200 mg, intravenously or placebo once every 3 weeks, plus chemotherapy (gemcitabine, 1 g/m², intravenously on days 1 and 8 and cisplatin, 80 mg/m², on day 1). Chemotherapy was administered once every 3 weeks for 4 to 6 cycles at the investigators’ discretion. Randomization, using interactive response technology, was stratified by sex and liver metastasis.

Participants in the tislelizumab plus chemotherapy arm could continue tislelizumab monotherapy beyond investigator-assessed progression. Participants in the placebo plus chemotherapy arm could cross over to tislelizumab monotherapy after independent review committee–confirmed progression.

Baseline Characteristics

The median age in both arms was 50 years (range, 23-74) and the majority (78.3%) of patients were male. Most participants (94.3%) were from China. Primary metastatic disease was present in 86 patients (32.7%), whereas 165 patients (62.7%) had recurrence after prior treatment for local disease. In the treatment arm, 61.1% of patients were ECOG performance status 1, whereas 65.2% were ECOG performance status 1 in the control arm.

The most common sites of metastases among patients in the treatment arm were the lymph nodes (67.2%), lung (46.6%), and bone (44.3%) compared with lymph nodes (55.3%), lung (47.7%), and bone (47.7%) in the control arm.

Safety

Treatment-emergent adverse events occurred in 133 of 133 participants (100%) in the tislelizumab arm and 120 of 130 participants (99.2%) in the placebo arm, with comparable grade 3 or higher adverse event rates. Immune-mediated adverse events were more frequent with tislelizumab (71 [53.4%] vs 49 [37.7%]) but mostly of grades 1 or 2. High B-cell gene expression was associated with greater OS benefit (HR, 0.41; 95% CI, 0.23-0.74).

Findings from a previous interim analysis of the trial also showed that tislelizumab had a safety profile consistent with prior known risks of the agent. No new safety signals were observed in the study.²

The investigators wrote that “after 3 years of follow-up, tislelizumab plus chemotherapy provided sustained PFS and meaningful OS improvement vs placebo plus chemotherapy in recurrent or metastatic NPC, with an acceptable safety profile.”

REFERENCE

1. Yang Y, Yen CJ, Pan J, et al. First-Line Tislelizumab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Cancer: Three-Year Follow-Up of the Phase 3 RATIONALE-309 Randomized Clinical Trial. JAMA Oncol. Published online February 26, 2026. doi:10.1001/jamaoncol.2026.0020

2. BeiGene Announces the Phase 3 RATIONALE 315 Trial Met Primary Endpoints of Major Pathological Response Rate and Event-Free Survival for Tislelizumab Plus Chemotherapy in Patients with Resectable Non-Small Cell Lung Cancer (NSCLC). News release. October 17, 2023. Accessed March 18, 2026. https://tinyurl.com/ddxxhf4u